Steroid sulfatase deficiency is a recently described, X-linked inborn error of metabolism. It is unique in that most of its manifestations occur prenatally. Women carrying affected fetuses have very low estriol production during pregnancy and usually fail to deliver infants vaginally. After birth, the only abnormality in these males that has been recognized to date is a lifelong dermatologic condition -ichthyosis. The research proposed will investigate the frequency of this biochemically unique form of ichthyosis among the many individuals reported to have this skin disease utilizing skin fibroblast assays of steroid sulfatase devised by the principal investigator. Endocrinologic evaluation of known patients will include steady state measurements of cholesterol sulfate, dehydroepiandrosterone sulfate, dehydroepiantrosterone, androstenedione, testosterone, estrone, estradiol, cortisol, FSH, and LH. Isotropic studies will evaluate androgen metabolism in these patients studying the conversion to dehydroepiandrosterone sulfate to dehydroepiandrosterone and thence to androstenedione and testosterone. Steroid sulfatase will be solubilized and purified from normal placentas and its properties carefully evaluated. The kinetics of substrate hydrolysis will be studied and the range of naturally occurring 3 OH steroid sulfates which may serve as substrates will be tested. The ability of a variety of naturally occuring and synthetic steroids to inhibit enzyme activity will also be considered in the hopes of developing a pharmacologically useful inhibitor of enzyme activity and hence of premature labor.